Project Summary/Abstract As highlighted by NCI, low human papillomavirus (HPV) vaccination rates represent a major lost opportunity for population-wide cancer prevention. Nearly all cervical cancer, 90% of anal cancers, ~60% of certain types of oropharyngeal cancers, and 40% of cancers of the vagina, vulva, and penis are caused by HPV, a sexually transmitted infection. Each year, 6.2 million persons are newly infected with HPV and 26,000 new HPV-related cancers are diagnosed, resulting in >$4 billion in annual medical expenses. HPV vaccination has extremely high efficacy in preventing vaccine strain-specific genital warts, adenocarcinoma in-situ, throat, anal, and cervical cancer, but low vaccination rates leave many individuals susceptible to HPV disease. National guidelines recommend vaccination of girls and boys starting at age 11yrs with 3 doses of HPV prior to onset of sexual activity. Still, in 2014, only 60% of 13-17yr girls and 42% of boys had even initiated the series. Pediatric primary care office visits are the main site for HPV vaccination, yet many missed opportunities (MOs) for vaccination occur in primary care and contribute to low vaccination rates. MOs are office visits during which a patient is eligible for a vaccine, but does not receive it. Many factors cause MOs-- provider factors (e.g., time-constrained visits, lack of communication skills, and giving vaccinations only at preventive visits) and parent factors (e.g., vaccine hesitancy). Immunization experts recommend multi-component interventions to prevent MOs and raise rates because they magnify the benefits of single-component interventions. However it is difficult to determine which components work in a multi-component intervention. We propose a multi-phase study that will first test the impact of 3 promising components, and then test the impact of a bundle of the 3. Our preliminary studies suggest that 3 interventions have promise in reducing MOs for HPV vaccination: training providers and office staff on HPV vaccine communication, prompts for providers to remind them to vaccinate eligible teens at any visit, and performance feedback to providers about their MOs. Working with a national network of primary care practices (60 practices for this study; >99,000 teens), we will test the impact of each intervention and then the impact of the bundle of 3 interventions on reducing MOs and improving HPV vaccine rates. Our study has 4 aims: Aim 1: Measure the effect of each component of STOP-HPV on: (a) MO rates and (b) HPV vaccination rates; Aim 2: Measure the effect of the 3-part bundle on: (a) MO rates and (b) HPV vaccination rates; Aim 3: Assess maintenance of the bundle following withdrawal of support from the research team and Aim 4: Measure implementation costs and cost-effectiveness of the interventions. We will then disseminate the most effective components nationally using the American Academy of Pediatrics' maintenance of certification program which is available to 64,000 pediatricians across the US.